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LABELED PKG-1-ALPHA-BINDING COMPOUNDS AND THEIR USE IN IMAGING AND QUANTIFYING PAIN

The present invention relates to the use of compounds that selectively bind to activated protein kinase G1 alpha for imaging the anatomic basis for chronic pain. Such imaging may also be used to objectively quantify chronic pain. Specifically, fluorine-18 and carbon -11 labeled NOP compouds, [18F] NOP46 and [11 C]NOP46, are disclosed for use as imaging agents for detecting and quantifying neuropathic pain.

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Reference:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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INDAZOLE DERIVATIVES AS SODIUM CHANNEL INHIBITORS

The invention relates to acyl sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to a new acyl sulfonamide Nav1.7 inhibitors of formula (I): or a pharmaceutically acceptable salt thereof, wherein U, V, W, X, Y, R and R1 are as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.

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Reference:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Design and synthesis of Rho kinase inhibitors (II)

In a previous study, we identified several structurally unrelated scaffolds of the Rho kinase inhibitor using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. 1H-Indazole is one of the candidate scaffolds on which a new series of potent Rho kinase inhibitors could be developed. In this study, the detailed structure-activity relationship of 1H-indazole analogues was studied. During this study, we found that the cell-free enzyme inhibitory potential of Rho kinase inhibitors having the 1H-indazole scaffold did not necessarily correlate with their inhibitory potential toward the chemotaxis of cultured cells. The choice of the linker substructure was shown to be an important factor for the 1H-indazole analogues to inhibit the chemotaxis of cells. Optimization of the 1H-indazole inhibitors with respect to the in vitro inhibition of monocyte chemotaxis induced by MCP-1 was carried out. The inhibitory potential was improved both in the cell-free enzyme assay and in the chemotaxis assay.

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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2-Aminothiadiazole inhibitors of AKT1 as potential cancer therapeutics

A series of 2-aminothiadiazole of inhibitors of AKT1 is described. SAR relationships are discussed, along with selectivity for protein kinase A (PKA) and cyclin-dependent kinase 2 (CDK2). Moderate selectivity observed in several compounds for AKT1 versus PKA is rationalized by X-ray crystallographic analysis. Key compounds showed activity in cellular assays measuring phosphorylation of two AKT substrates, PRAS40 and FKHRL1. Compound 30 was advanced to a mouse liver PD assay, where it showed dose-dependent inhibition of AKT activity, as measured by the inhibition of phospho-PRAS40.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

Can You Really Do Chemisty Experiments About Methyl 4-bromobenzo[b]thiophene-2-carboxylate

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Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. In heterogeneous catalysis, catalysts provide a surface to which reactants bind in a process of adsorption. 360575-29-7, name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate. In an article£¬Which mentioned a new discovery about 360575-29-7, Recommanded Product: 360575-29-7.

Heteroaryl hydroxycarbonylation: An efficient, robust, practically scalable approach using formyl acetate as the co source

A simple, efficient, regioselective, and scalable palladium-catalyzed hydroxycarbonylation of heteroaryl halides to corresponding carboxylic acids using acetic-formic anhydride in presence of Pd(OAc)2, dppf, and diisopropylethyl amine in dimethyl formamide at 80-90 C in excellent yields. Taylor & Francis Group, LLC.

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. In heterogeneous catalysis, catalysts provide a surface to which reactants bind in a process of adsorption. 360575-29-7, name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate. In an article£¬Which mentioned a new discovery about 360575-29-7, Formula: C10H7BrO2S.

Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5- carboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)

Potent, 1H-pyrazolo[3,4-b]pyridine-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using structure-based design techniques. Many of these compounds exhibited nanomolar antiproliferation activities against human tumor lines in in vitro cell culture experiments, and a representative example (compound 26) demonstrated encouraging in vivo efficacy in a mouse xenograft tumor model derived from the A2780 cell line. This molecule also exhibited reduced rat retinal exposures relative to a previously studied imidazo-pyridine-containing NAMPT inhibitor. Somewhat surprisingly, compound 26 was only weakly active in vitro against mouse and monkey tumor cell lines even though it was a potent inhibitor of NAMPT enzymes derived from these species. The compound also exhibited only minimal effects on in vivo NAD levels in mice, and these changes were considerably less profound than those produced by an imidazo-pyridine-containing NAMPT inhibitor. The crystal structures of compound 26 and the corresponding PRPP-derived ribose adduct in complex with NAMPT were also obtained.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Chemistry is traditionally divided into organic and inorganic chemistry. category: benzothiophene, The former is the study of compounds containing at least one carbon-hydrogen bonds.In a patent£¬Which mentioned a new discovery about 360575-29-7

Maximizing lipophilic efficiency: The use of Free-Wilson analysis in the design of inhibitors of acetyl-CoA carboxylase

This paper describes the design and synthesis of a novel series of dual inhibitors of acetyl-CoA carboxylase 1 and 2 (ACC1 and ACC2). Key findings include the discovery of an initial lead that was modestly potent and subsequent medicinal chemistry optimization with a focus on lipophilic efficiency (LipE) to balance overall druglike properties. Free-Wilson methodology provided a clear breakdown of the contributions of specific structural elements to the overall LipE, a rationale for prioritization of virtual compounds for synthesis, and a highly successful prediction of the LipE of the resulting analogues. Further preclinical assays, including in vivo malonyl-CoA reduction in both rat liver (ACC1) and rat muscle (ACC2), identified an advanced analogue that progressed to regulatory toxicity studies.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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As an important bridge between the micro and macro material world, chemistry is one of the main methods and means for humans to understand and transform the material world. 360575-29-7, name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate. In an article£¬Which mentioned a new discovery about 360575-29-7, Recommanded Product: 360575-29-7.

Synthesis of 7-oxo-dihydrospiro[indazole-5,4?-piperidine] acetyl-CoA carboxylase inhibitors

Synthesis of oxo-dihydrospiroindazole-based acetyl-CoA carboxylase (ACC) inhibitors is reported. The dihydrospiroindazoles were assembled in a regioselective manner in six steps from substituted hydrazines and protected 4-formylpiperidine. Enhanced regioselectivity in the condensation between a keto enamine and substituted hydrazines was observed when using toluene as the solvent, leading to selective formation of 1-substituted spiroindazoles. The 2-substituted spiroindazoles were formed selectively from alkyl hydrazones by ring closure with Vilsmeier reagent. The key step in the elaboration to the final products is the conversion of an intermediate olefin to the desired ketone through elimination of HBr from an O-methyl bromohydrin. This methodology enabled the synthesis of each desired regioisomer on 50-75 g scale with minimal purification. Acylation of the resultant spirocyclic amines provided potent ACC inhibitors.

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Rational drug design of indazole-based diarylurea derivatives as anticancer agents

A series of novel indazole-based diarylurea derivatives targeting c-kit were designed by structure-based drug design. The derivatives were prepared, and their antiproliferative activities were evaluated against human colon cancer HCT-116 cell line and hepatocellular carcinoma PLC/PRF/5 cell line. The antiproliferative activities demonstrated that six of nine compounds exhibited comparable activities with sorafenib against HCT-116. The structure?activity relationship (SAR) analysis indicated that the indazole ring part tolerated different kinds of substituents, and the N position of the central pyridine ring played key roles in antiproliferative activity. The SAR and interaction mechanisms were further explored using molecular docking method. Compound 1i with N-(2-(pyrrolidin-1-yl)ethyl)-carboxamide possessed improved solubility, 596.1?ng/ml and best activities, IC50 at 1.0?mum against HCT-116, and 3.48?mum against PLC/PRF/5. It is a promising anticancer agent for further development.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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360575-29-7, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 360575-29-7, molcular formula is C10H7BrO2S, introducing its new discovery.

SUBSTITUTED CONDENSED PYRIMIDINE COMPOUNDS

The invention relates to novel substituted condensed pyrimidine compounds of general formula (I) in which the chemical groupings, substituents and indices are as defined in the description, and to their use as medicaments, in particular as medicaments for the treatment of conditions and diseases that can be treated by inhibition of the PDE4 enzyme.

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem